title: Crystal structure and physicochemical properties of crystalline form of 2'-O-{3-[(7-chloro-4-quinolinyl)amino]propyl}-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A.
abstract: The intent of the study was to prepare and characterize crystalline form of 2'-O-{3-[(7-chloro-4-quinolinyl)amino]propyl}-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A (1), a novel 15-membered azalide derivative with antimalarial activity. The crystalline material was prepared by crystallization from acetonitrile reproducible in high yield and purity. Single crystal X-ray studies, X-ray powder diffractometry, differential scanning calorimetry, thermogravimetric analysis, moisture adsorption, Karl Fischer titration, gas chromatography, scanning electron microscopy, optical microscopy, solubility, and solid-state and solution stability were conducted to investigate physicochemical properties of the existing crystalline form. Crystalline 1 is not hygroscopic, does not contain solvents, is physicochemically stable in solid state for up to 4 weeks, and is highly soluble at pH values below 6 and in biorelevant media (simulated gastric fluid, fed simulated intestinal fluid, and fasted simulated intestinal fluid). Solution stability studies (buffers and biorelevant media) indicated that this compound is stable in solutions at pH values 5-6, and that stability is influenced by pH and temperature.
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd., Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. darko.filic@glpg.com
authors.forename: Darko
authors.initials: D
authors.lastname: Filić
authors.forename: Kristina
authors.initials: K
authors.lastname: Starčević
authors.forename: Dijana
authors.initials: D
authors.lastname: Pešić
authors.forename: Stella
authors.initials: S
authors.lastname: Jurmanović
authors.forename: Eugene
authors.initials: E
authors.lastname: Meenan
authors.forename: Alberto
authors.initials: A
authors.lastname: Spezzaferri
authors.forename: Ivica
authors.initials: I
authors.lastname: Đilović
authors.forename: Biserka
authors.initials: B
authors.lastname: Prugovečki
mesh_terms: D000327:Adsorption; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry*; D002021:Buffers; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004355:Drug Stability; D004917:Erythromycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D005750:Gastric Juice / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007419:Intestinal Secretions / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D033362:Powder Diffraction; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013818:Thermogravimetry; D044366:Transition Temperature; D014867:Water / Q000737:chemistry
chemical_list: D000962:Antimalarials; D002021:Buffers; D014867:Water; D004917:Erythromycin